8 S U P P L E M E N T T O O U T P A T I E N T S U R G E R Y M A G A Z I N E J U LY 2 0 1 5
ure out the best dose of Exparel, compared the drug at several dose levels to
bupivacaine HCl 150 mg. The researchers found no appreciable differences in
visual analog pain scores until they cranked up the dosage of Exparel to 533 mg,
more than double the dosage of the control. At that level, Exparel patients expe-
rienced a very high level of adverse events — 78% experienced nausea, 48%
experienced hemorrhagic anemia and 20% experienced anemia. Exparel's ulti-
mate approval was for no more than 20 mL, or 266 mg, and that is what comes
in each $285 vial.
A study of 136 breast augmentation patients randomized to bupivacaine or
Exparel appears to have produced a slight edge for Exparel in a measurement
called "area under the curve." Exparel patients' pain scores were about 6%
lower than bupivacaine's, but the authors admit that the study was "underpow-
ered." And in the study, Exparel test subjects received a 300 mg dose, whereas
bupivacaine controls received only a 100 mg dose.
"These were not robust trial results," says an anesthesiologist with knowledge of
Exparel's development program who spoke on the condition of anonymity, "and a
number of trials had negative findings."
With Phase 2 complete, the company moved on to Phase 3 studies, which it
would use to prove safety and efficacy to the FDA. Unlike most earlier studies,
FDA reviewers vetted the results of these studies. Here are the 3 studies and
what they found:
• A study pitting Exparel against saline in hemorrhoidectomy surgery found
that Exparel was more effective than saline at controlling pain for up to 24
hours, at which point its efficacy was indistinguishable from placebo. "The anal-
gesia derived from Exparel does not differ from placebo, at least not in a clini-
cally meaningful way, beyond 24 hours," wrote FDA reviewer Arthur Simone,
MD, PhD.
• A study pitting Exparel against saline in bunionectomy surgery found that
Exparel was more effective than saline for 12 hours. Somewhere between 12 and
24 hours, the differences became statistically insignificant. Both Exparel and
